title: Genetic and clinical markers of elevated liver fat content in overweight and obese Hispanic children.
abstract: OBJECTIVE
  Genetic variation in six genes has been associated with elevated liver fat and nonalcoholic fatty liver disease in adults. The influence of these genes on liver fat and whether a genetic risk score (GRS) would improve upon the ability of common clinical risk factors to predict elevated liver fat content (ELF) in Hispanic children was determined.
  
  
  METHODS
  223 obese Hispanic children were genotyped for six SNPs. MRI was used to measure liver fat. A GRS was tested for association with ELF using multivariate linear regression. Predictors were assessed via ROC curves and pair-wise analysis was used to determine significance alone and combined with clinical markers.
  
  
  RESULTS
  Only variants in PNPLA3 and APOC3 genes were associated with liver fat (P < 0.001, P = 0.01, respectively). Subjects with a GRS = 4 had ∼3-fold higher liver fat content than subjects with GRS of 0 (15.1 ± 12.7 vs. 5.1 ± 3.7%, P = 0.03). While the addition of the GRS to a model containing BMI and liver enzymes increased ROC AUC from 0.83 to 0.85 [95% CI, 0.79-0.89], (P = 0.01), it does not improve detection of ELF from a clinical perspective.
  
  
  CONCLUSIONS
  Only PNPLA3 and APOC3 were related to ELF and a GRS comprised of these susceptibility alleles did not add to the discriminatory power of traditional biomarkers for clinical assessment of liver fat.
authors.affiliation: Department of Preventive Medicine, University of Southern California, Keck School of Medicine, Los Angeles, USA.
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Walker
authors.forename: Frank
authors.initials: F
authors.lastname: Sinatra
authors.forename: Jaana
authors.initials: J
authors.lastname: Hartiala
authors.forename: Marc
authors.initials: M
authors.lastname: Weigensberg
authors.forename: Donna
authors.initials: D
authors.lastname: Spruijt-Metz
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Alderete
authors.forename: Michael I
authors.initials: MI
authors.lastname: Goran
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
mesh_terms: D000293:Adolescent; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D000886:Anthropometry; D053305:Apolipoprotein C-III / Q000235:genetics / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D015992:Body Mass Index; D002648:Child; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000235:genetics*; D050177:Overweight / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D053305:Apolipoprotein C-III; D001219:Aspartate Aminotransferases; D001786:Blood Glucose; D008049:Lipase; D008565:Membrane Proteins; D014280:Triglycerides; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent